CX3CR1

Chr 3

C-X3-C motif chemokine receptor 1

Also known as: CCRL1, CMKBRL1, CMKDR1, GPR13, GPRV28, V28

NCBI Gene: 1524ENSG00000168329UniProt: P49238OMIM: 601470

The CX3CR1 protein is a receptor for the chemokine fractalkine that regulates immune cell migration, inflammation, and microglial function in the brain including synaptic pruning during development. Mutations cause immunodeficiency and increased susceptibility to invasive fungal infections, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants (pLI 0.06, LOEUF 1.01), consistent with recessive inheritance requiring biallelic mutations for disease.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.013 OMIM phenotypes
Clinical Summary— CX3CR1
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Population Constraint (gnomAD)
Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 37 VUS of 62 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — CX3CR1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.061
Z-score 1.56
OE 0.39 (0.18–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.08Z-score
OE missense 0.79 (0.69–0.90)
162 obs / 205.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.39 (0.18–1.01)
0≤0.351.4
Missense OE0.79 (0.69–0.90)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 3 / 7.7Missense obs/exp: 162 / 205.6Syn Z: -0.94
DN
0.80top 10%
GOF
0.81top 10%
LOF
0.1796th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

62 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS37
Likely Benign10
Benign3
8
Pathogenic
1
Likely Pathogenic
37
VUS
10
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
37
0
0
37
Likely Benign
0
4
0
6
10
Benign
0
1
0
2
3
Total0429859

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CX3CR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
CX3CR1+ synovial macrophages accumulate in the joint during experimental hemophilic arthropathy but are not required for acute synovitis.
Lawrence AG et al.·J Thromb Haemost
2026
Bisphenol A potentiates ischemia-reperfusion-induced endothelial and blood-brain barrier dysfunction associated with CX3CL1-CX3CR1 signaling.
Zhou K et al.·Ecotoxicol Environ Saf
2026
Correction: Iwahashi et al. Pathophysiological Roles of the CX3CL1-CX3CR1 Axis in Renal Disease, Cardiovascular Disease, and Cancer. Int. J. Mol. Sci. 2025, 26, 5352.
Iwahashi Y et al.·Int J Mol Sci
2026
Abnormal FKN-CX3CR1-NR signal triggers hippocampal synaptic dysfunction in rheumatoid arthritis-related depression.
Yao SX et al.·Int Immunopharmacol
2026
Targeting CX3CR1 inhibits silica-induced epithelial-mesenchymal transition and pulmonary fibrosis in mice via the NF-κB signaling pathway.
Zhang J et al.·Toxicology
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients